shikonin and Adenocarcinoma

Shikonin, a small-molecule natural product which inhibits the activity of pyruvate kinase M2 (PKM2), has been studied as an anti-cancer drug candidate in human cancer models. Here, our results demonstrate that shikonin is able to sensitize human breast cancer cells to chemotherapy by paclitaxel (taxol). Human breast adenocarcinoma MBA-MD-231 cells, which have higher levels of PKM2 expression and activity compared with MCF-7 cells, were selected to study further. The concentrations of shikonin and taxol were first selected at which they did not significantly induce cytotoxicity when treated alone, whereas the combination induced apoptosis. Surprisingly, PKM2 activity was decreased by shikonin, but not by the combination treatment. To identify the potential targets of this combination, human phospho-kinase antibody array analysis was performed and results indicated that the combination treatment inhibited the activation of ERK, Akt, and p70S6 kinases, which are known to contribute to breast cancer progression. Finally, how the combination affects breast cancer cell growth in vivo was tested using a xenograft tumor model. The results indicated that shikonin plus taxol prolonged animal survival and reduced tumor size than the vehicle treatment group. In summary, our results suggest that shikonin has a potential as an adjuvant for breast cancer therapy.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Drug Interactions; Drug Therapy, Combination; Female; Heterografts; Humans; Mice; Mice, Nude; Naphthoquinones; Paclitaxel

Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, can exert inhibitory effect on tumor cell growth. However, little has been known concerning the effect of shikonin on lung adenocarcinoma cell and underlying mechanisms. In the present study, we investigated the effect of shikonin on the proliferation, cell cycle arrest, and apoptosis in human lung adenocarcinoma cells. We found that shikonin significantly suppressed the proliferation of lung adenocarcinoma cells compared with control in dose- and time-dependent manner (P < 0.05). In the meantime, our results showed that shikonin markedly increased the proportion of A549 cells at stage G1 as well as induced apoptosis in A549 cells. Furthermore, suppressed CCND1 and elevated caspase3 and caspase7 expression levels at mRNA were found in this study, indicating that shikonin may inhibit the growth of lung adenocarcinoma cell by changing cell cycle and promoting cell apoptosis through the regulation of CCND1, caspase3, and caspase7. Although more studies are needed, this study suggests that shikonin has the potential to be used as an anti-cancer agent in the treatment of lung adenocarcinoma.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents; Apoptosis; Caspases; Cell Line, Tumor; Cell Proliferation; Enzyme Activation; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Naphthoquinones; Resting Phase, Cell Cycle

The shikonin mixture was used for 19 cases of later-stage lung cancer who were not the candidates for operation, radiotherapy and chemotherapy. The clinical observation showed that shikonin mixture could inhibit the growth of lung cancer and improve the immune function of the body. The tumors were reduced over 25% in diameter. The effective rate was 63.3%, remission rate 36.9%, survival rate of one year 47.3%. The intermedium survival period was about 10 months, including adenocarcinoma 10 months, squamous carcinoma 12 months. After treatment the life quality of patients were greatly improved. The patients got better appetite and their body weights were increased. They could manage themselves in daily life. The Karnofsky scores were enhanced by 20. The authors also observed that shikonin mixture could relieve such symptoms as cough, bloody sputum and chest pain caused by lung cancer. The levels of cells and interleukin-2 were increased (P less than 0.001). It had no harmful effects on peripheral blood picture, heart, kidney and liver. Shikonin mixture is safe and effective for later-stage cancer.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Phytogenic; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Female; Ginsenosides; Humans; Interleukin-2; Killer Cells, Natural; Lung Neoplasms; Male; Middle Aged; Naphthoquinones; Saponins